Synthetic
peptides related to
amino acid residues 29-42 of human
serum amyloid A (SAA), Tyr-Ile-Gly-Ser-
Asp-Lys-Tyr-
Phe-His-Ala-Arg-Gly-Asn-Tyr, were found to inhibit the adhesion of human T-lymphocytes and of mouse M4
melanoma cells to surfaces coated with the major cell adhesive
glycoproteins of the extracellular matrix,
laminin or
fibronectin. Correspondingly inhibitory activity was manifested by the entire 14-residue
peptide, by its YIGSD
laminin-related domain, and by RGN, the
fibronectin-related domain. Intact recombinant SAA (rSAA) and its 1-76 fragment, an
amyloid A (AA)
protein, also inhibited cell adhesion. The
peptides did not inhibit
collagen and
ADP-induced aggregation of human platelets. Proteolysis of SAA by lysosomal
enzymes originating from human neutrophils led to generation of specific
peptide segments some of which pertain to the 29-42 domain. It is suggested that the
acute-phase protein SAA might be involved, either directly or via its
peptide fragments, in inhibition of inflammatory reactions or metastatic processes which depend on
integrin and possibly other extracellular-matrix-specific receptors mediated specific recognition and interactions with immobilized components of blood-vessel walls.